Microbial Metabolomics: A Search for the Missing Link to Cancer

Jane De Lartigue, PhD

Published: Friday, Feb 08, 2019

The microbes that inhabit the epithelial surfaces of our body, known collectively as the microbiota, vastly outnumber our own cells and genetic material. They have piqued scientific interest since their discovery in the mid-880s.

Thanks to technological advances, the past several decades have witnessed a blossoming appreciation of the varied composition of these microbial communities, their complex and dynamic relationship with the host, and the way they affect health and disease.

Investigators have focused on the gut microbiota, which make up the bulk of an individual’s bacterial ecosystem. It has become increasingly apparent that a complex interplay between the bacteria, the intestinal epithelium, and the immune system can be beneficial. Consequently, changes in the types of bacteria that make up the microbiota can disrupt this mutualistic relationship and have long been associated with the development of various disease states, including cancer.

Despite clear evidence of a link between the microbiota and cancer, it remains unclear whether this is causal or consequential. Understanding how the microbiome functionally influences disease is the critical missing link, and the application of metabolomics could be one of the keys to deciphering it.

Studies have revealed metabolic “chatter” between the host and their microbiota, with both producing a wide variety of metabolites that have a breadth of influence, including potentially driving carcinogenesis.

Although the science is in its infancy, research that hones our understanding of microbial metabolomic profiles could allow earlier diagnosis of disease and the development of new prognostic biomarkers for cancer types that are desperately lacking in these areas. New therapeutic strategies aimed at manipulating the microbiota also offer a unique and potentially promising avenue of research.

The Ecological Niche Within

The first recorded observations of bacteria in the intestines of healthy individuals were made more than a century ago.1 Since then there has been a growing appreciation of the extent of this intestinal ecosystem and its impact on human health. Ultimately, at the turn of the millennium, advances in genome sequencing and research initiatives, such as the National Institutes of Health’s Human Microbiome Project, propelled the microbiota into an exciting new era at the forefront of contemporary medicine.2

The microbial cells in our body outnumber our own cells by as many as 10 to 1 and have staggering genetic diversity in their microbiome. More than 1000 species fall into 2 major phyla: bacteroidetes and firmicutes. They line all epithelial barriers, including the skin, mouth, and vagina, but the majority are found in the gastrointestinal (GI) tract.3-5

These bacteria begin to colonize humans before birth through the amniotic fluid, placenta, and umbilical cord blood. Transmission from the mother continues upon passage through the birth canal, and the microbiota mature and develop through the influence of breast milk or formula and the introduction of solid foods.6

The microbiota are often described as having a “commensal” relationship with the host, meaning that they cause neither harm nor benefit. However, as our understanding has evolved, it has become clear that they form vital components of the intestinal epithelium and contribute to the health of their human host by performing important physiological functions, including harvesting inaccessible nutrients from food, generating energy, and regulating the immune response.

Collectively, they form a dynamic ecosystem of bacterial communities throughout the body, the composition of which varies depending on many factors, such as the surrounding environmental conditions, drug usage, and—garnering the most mainstream attention—diet.7

Our ability to determine the composition of the microbiota and how this changes under different conditions is directly attributable to the development of faster and cheaper technologies for the sequencing of the 16S ribosomal RNA gene. Encoding a subunit of the prokaryotic ribosome, this gene is universally expressed and highly conserved across bacterial species, except for a hypervariable region that is species specific.8,9

Dysbiosis in Cancer

Some changes in the microbiota create an imbalance in their mutualistic relationship, known as dysbiosis, which can have negative consequences for the host. A growing body of evidence indicates a link between dysbiosis and the development of disease, including various types of cancer.7

The association between gut bacteria and cancer predates our understanding of the microbiota. Certain infectious bacteria, such as Heliobacter pylori, which cause one of the most prevalent infections in the world, can predispose patients to the development of gastric cancer. Both the presence of H pylori and attempts to treat it can lead to dysbiosis of the GI microbiota.10-14